Altered B cell activation contributes to the immunopathogenesis of childhood arthritis-associated uveitis

In Juvenile Idiopathic Arthritis (JIA), the most common childhood rheumatic disease, many patients also develop uveitis (JIA-uveitis), risking life-long vision loss. The mechanisms driving uveitis development in JIA remain understudied. Here, we demonstrate that peripheral blood CD19⁺IgD^-CD27^- double negative type 1 (DN1) B cells are elevated in JIA-uveitis compared to JIA patients without eye disease (JIA). The B cell receptor (BCR) repertoire was also more clonal and somatically hypermutated in JIA-uveitis and antigen-activated B cells infiltrated chronically inflamed JIA-uveitis eyes. Features of heightened B cell activation were recapitulated in experimental autoimmune uveoretinitis (EAU) and disrupting B and T cell interactions using monoclonal antibodies and transgenic mice suppresses uveitis. Together, these findings support a conceptual shift that uveitis is a primarily T cell driven disease and provide evidence for potential new therapeutic strategies that also consider B cells as drivers in disease pathology.